免疫性疾病中抗肿瘤坏死因子抑制剂治疗后炎症性中枢神经系统疾病的风险：系统综述与Meta分析

肿瘤坏死因子（TNF）抑制剂已被广泛用于治疗各种自身免疫性疾病。然而，关于TNF抑制剂治疗后炎症性中枢神经系统（CNS）疾病事件的风险仍存在争议，同时对于这一风险在不同自身免疫性疾病或不同的TNF阻断剂之间的变异性尚存不确定性。本文旨在评估抗TNF治疗后炎症性CNS疾病的风险，并比较不同基础自身免疫性疾病或TNF抑制剂之间的风险差异。我们在PubMed、Embase和Cochrane图书馆中，从数据库建立之初至2024年3月1日进行检索。纳入的研究为观察性研究，旨在评估抗TNF治疗与炎症性CNS疾病发生之间的关联，比较组为对照组。研究的筛选和数据提取由两名研究者遵循PRISMA指南独立完成。采用风险比（RR）作为合并分析的效应指标。主要结局为抗TNF治疗后自身免疫性疾病中新发炎症性CNS事件的风险。次级分析根据不同基础自身免疫疾病类型和TNF抑制剂进行。共纳入18项研究，涉及1,118,428名自身免疫性疾病患者，随访总人年超过5,698,532人年。TNF抑制剂启动后新发炎症性CNS事件的发病率范围为每10,000人年2.0至13.4例。总体来看，与传统治疗相比，暴露于TNF抑制剂与任何炎症性CNS疾病风险增加36%相关（RR，1.36；95% CI，1.01-1.84；I2，49%），主要归因于脱髓鞘疾病（RR，1.38；95% CI，1.04-1.81；I2，31%）。次级分析显示，不同基础自身免疫疾病类型（风湿性疾病：RR，1.36；95% CI，0.84-2.21；炎症性肠病：RR，1.49；95% CI，0.93-2.40；子群P值=0.74）以及不同TNF抑制剂（抗TNF单克隆抗体与依那普利：RR，1.04；95% CI，0.93-1.15；I2，0%）之间炎症性CNS疾病的风险类似。综上，与传统治疗相比，暴露于TNF抑制剂会增加36%的炎症性CNS疾病风险，无论基础疾病类型或TNF抑制剂类型如何。

Tumor necrosis factor (TNF) inhibitors have been used extensively to treat various autoimmune diseases. However, there are ongoing debates about the risk of inflammatory central nervous system (CNS) disease events following TNF inhibitor therapy, as well as uncertainty about how this risk varies across different autoimmune diseases or TNF-blocking agents.To evaluate the risk of inflammatory CNS diseases after anti-TNF initiation and assess the difference in risk among different types of underlying autoimmune diseases or TNF inhibitors.Separate searches were conducted across PubMed, Embase, and the Cochrane Library from inception until March 1, 2024.Observational studies assessing the association between anti-TNF therapy and inflammatory CNS diseases relative to a comparator group.Study eligibility assessment and data extraction were independently conducted by 2 investigators following PRISMA guidelines. The risk ratio (RR) was used as the effect measure of the pooled analysis.The primary outcome was the risk of incident inflammatory CNS events after anti-TNF therapy for autoimmune diseases. Secondary analyses were performed based on different types of underlying autoimmune diseases and TNF inhibitors.Eighteen studies involving 1 118 428 patients with autoimmune diseases contributing more than 5 698 532 person-years of follow-up were analyzed. The incidence rates of new-onset inflammatory CNS events after initiating TNF inhibitors ranged from 2.0 to 13.4 per 10 000 person-years. Overall, exposure to TNF inhibitors was associated with a 36% increased risk of any inflammatory CNS disease compared to conventional therapies (RR, 1.36; 95% CI, 1.01-1.84; I2, 49%), mainly attributed to demyelinating diseases (RR, 1.38; 95% CI, 1.04-1.81; I2, 31%). Secondary analyses revealed a similar risk of inflammatory CNS diseases across different types of underlying autoimmune diseases (rheumatic diseases: RR, 1.36; 95% CI, 0.84-2.21; inflammatory bowel disease 1.49; 95% CI, 0.93-2.40; P for subgroup = .74) and TNF inhibitors (anti-TNF monoclonal antibodies vs etanercept: RR, 1.04; 95% CI, 0.93-1.15; I2, 0%).Compared to conventional therapies, exposure to TNF inhibitors was associated with a 36% increased risk of inflammatory CNS diseases, irrespective of background autoimmune disease or TNF inhibitor type.